DCs 'Tip' off the innate immune system

The role of dendritic cells (DCs) in adaptive immune responses is well established, but do these cells have a direct role in innate immune defence? A recent study, published in Immunity, identified a subset of DCs termed Tip-DCs (tumour-necrosis factor (TNF)/ inducible nitric oxide synthase (iNOS)-producing DCs) that are essential for host defence against bacterial infections.

To investigate which cells are involved in the clearance of bacteria, Serbina and colleagues infected wild-type mice and mice that lacked expression of the chemokine receptor CCR2 with Listeria monocytogenes. Previous studies have shown that CCR2 targets monocytes to sites of inflammation and that Ccr2^−/− mice are unable to control bacterial infections in vivo. Initially, the numbers of L. monocytogenes were similar in the wild-type and Ccr2^−/− mice, but after 48 hours, the wild-type mice had begun to clear the infection, whereas the bacterial load kept increasing in the Ccr2^−/− mice.

Immunohistological examination of the spleens from these mutant mice showed normal localization of L. monocytogenes and Mac3⁺ (a marker expressed by some DCs and activated macrophages) cells to T-cell areas of the spleen, and the pattern of DEC205⁺ DCs was also similar to that seen in wild-type mice. However, the Ccr2^−/− mice lacked a population of cells with intermediate expression of CDllb and CDllc that was present in their wild-type counterparts.

What role do these CDllb^midCDllc^mid cells have in the clearance of bacterial infections? T-cell responses to L. monocytogenes seemed to be normal in the Ccr2^−/− mice, showing that the central role of these cells is not in T-cell priming. Further experiments showed that the CDllb^midCDllc^mid DCs that are lacking in Ccr2^−/− mice are the main sources of TNF and iNOS (which catalyses the synthesis of NO, a central mediator of bacterial killing) within the first 48 hours of bacterial infections, hence their name of Tip-DCs.

Early control of L. monocytogenes infection, therefore, requires the presence of Tip-DCs, which are probably recruited to the spleen by CCR2 signalling, so confirming a direct role for DCs in innate immune responses against microbial pathogens.